This laboratory has evaluated the stress dependence of connective tissue in a series of studies over the past several years. The cumulative data from these papers support the extension of Wolff's law to fibrous connective tissue and other specialized connective tissues as well. Effects of stress changes are seen with exercise, stress deprivation and repair. Current evidence suggests that stress deprivation causes profound and rapid deterioration of fibrous tissues. Early results suggest that the recovery rate of ligament substance roughly parallels the degradation rate. Insertion site weakness also results from stress deprivation. This change results from osteoclastic resorption of the ligamentous attachment fibers, along with resorption of bone at these sites. Recovery from ligament insertion weakness appears to be a very slow process, requiring more than a year to overcome changes induced in 2-3 months. The purpose of the proposed research program is to document more completely: 1) the fibrous connective tissue and insertion site morphological and biochemical changes resulting from stress deprivation, and 2) the consequent alteration in physical characteristics. The answers to these questions are particularly important with respect to the development of the rationale for treatment and rehabilitation of soft tissue injuries, such as the knee ligaments, etc. A standard internal fixation model will be used to induce stress deprivation effects in rabbit knees. Capsular and ligamentous structures from the model will be characterized by biomechanical, morphological, biochemical and metabolic techniques on a progressive time base during the development of and during recovery from the stress deprivation state. Preliminary results indicate the need to follow the animals for more than one year because of the slow recovery rate. Finally, hormone or drug treatment effects will be evaluated for efficacy in modulating the development and recovery from the stress deprivation state. Biochemical analyses to be employed will permit evaluation of collagen turnover, total proteoglycans, and collagen cross-link quantitation (reducible and non-reducible). Light microscopy and transmission EM will be used to characterize matrix and cells, as well as the ligament insertion sites. Biomechanical tests will yield data on ultimate strength and stiffness of bone-ligament-bone complex, as well as the mechanical properties of the ligament substance. In addition, arthrographic characterization of contracture strength will also be performed.